As more drugs and treatments are becoming available for the chemotherapy of the cancer patient, individual variability in responses to drugs becomes more apparent. In most cases, it is not clear why only a certain percentage of patients with a given tumor type will respond to a specific treatment, nor is it known a priori what alternative treatment could be given to a patient who is not responding to the primary treatment of choice or who has become resistant to it. Thus, considering the relatively potent but poorly selective anticancer drugs available, it would be very important to be able to assess the sensitivity of a drug in the individual tumor type. During the last two years, studies have been initiated both in man and in animal tumor models to understand the biochemical basis of drug selectivity. Studies such as drug uptake, activation and their incorporation into nucleic acid and intracellular concentration and retention of the active metabolite were carried out. Furthermore, the relative role of the de novo and salvage pathways for synthesis of nucleic acid precursors have also been evaluated. Experiments have also been initiated to modify the cytotoxicity of antimetabolites by the co-administration of normal metabolites in vivo.